[unreadable] The long-term goals of the proposed research are to improve the acquisition, reconstruction, and extraction of quantitative information from SPECT images of medium-energy radionuclides, and to assess these improvements to the imaging system using task-dependent criteria. Medium-energy radionuclides are becoming increasingly important for the diagnosis, staging, and treatment of cancer. During the first project period, we focused our attention on improving collimation and corrections for scatter and nonuniform attenuation for Ga-67 SPECT imaging, as well as on enhancing our techniques for Monte Carlo simulation of medium-energy photons. In this renewal application, we turn our attention to similar improvements to SPECT imaging of other medium-energy radionuclides, such as In-111, Lu-177, and Cu-67, that are playing an increasing role in cancer diagnosis and therapy. We will construct and evaluate new collimators, designed for Ga-67 during the previous funding period, and design, construct, and evaluate new collimation for In-111. Our experience in simultaneous dual-isotope SPECT imaging will be extended to radionuclide pairs that include medium-energy photon emitters. We will develop a new joint iterative algorithm, based on very rapid Monte Carlo simulation of scatter, crosstalk, and lead x-rays in several energy windows, to correct simultaneously for these phenomena on SPECT images of isotopes emitting multiple decay photons, as well as to accomplish simultaneous imaging of dual-isotope pairs. We will measure, using simulated data, as well as phantom and patient data, the improvements in activity and size estimation due to improved imaging procedures, and compare the performance achieved to theoretical bounds. We will also compare the utility of several gamma/beta-emitting nuclides (or nuclide pairs) on the basis of the accuracy with which radioimmunotherapy dosimetry can be accomplished. The feasibility of our simultaneous dual-isotope procedures will be evaluated on the basis of performance in two clinical tasks using patient images. The first is prediction of progression from low-grade to higher-grade NHL using simultaneous imaging of Ga-67 and TI-201, and the second is diagnosis of vertebral osteomyelitis based on simultaneous imaging of Ga-67 and Tc-99m-MDP. We expect that the imaging system improvements that will be accomplished during the proposed project period will lead to more accurate diagnosis, staging, and/or treatment of patients and, consequently, improved patient care. [unreadable] [unreadable]